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Tuesday, December 16, 2008

The Sanger Method of DNA Sequencing

 
In 1976 Frederick Sanger developed a method for sequencing DNA enzymatically using the Klenow fragment of E. coli DNA polymerase I. Sanger was awarded his second Nobel Prize for this achievement (he received his first Nobel Prize for developing a method for sequencing proteins). The advantage of using the Klenow fragment for this type of reaction is that the enzyme lacks the 5′ → 3′ exonuclease activity, which could degrade newly synthesized DNA. However, one of the disadvantages is that the Klenow fragment is not very processive and is easily inhibited by the presence of secondary structure in the single-stranded DNA template. This limitation can be overcome by adding SSB or analogous proteins, or more commonly, by using DNA polymerases from bacteria that grow at high temperatures. Such polymerases are active at 60° to 70°C, a temperature at which secondary structure in single-stranded DNA is unstable.

The Sanger sequencing method uses 2′,3′-dideoxynucleoside triphosphates (ddNTPs), which differ from the deoxyribonucleotide substrates of DNA synthesis by lacking a 3′-hydroxyl group (see below). The dideoxyribonucleotides, which can serve as substrates for DNA polymerase, are added to the 3′ end of the growing chain. Because these nucleotides lack a 3′-hydroxyl group, subsequent nucleotide additions cannot take place and incorporation of a dideoxynucleotide terminates the growth of the DNA chain. When a small amount of a particular dideoxyribonucleotide is included in a DNA synthesis reaction, it is occasionally incorporated in place of the corresponding dNTP, immediately terminating replication. The length of the resulting fragment of DNA identifies the position of the nucleotide that should have been incorporated.

Chemical structure of a 2′,3′-dideoxynucleoside triphosphate.
B represents any base.
DNA sequencing using ddNTP molecules involves several steps (as shown below). The DNA is prepared as single-stranded molecules and mixed with a short oligonucleotide complementary to the 3′ end of the DNA to be sequenced. This oligonucleotide acts as a primer for DNA synthesis catalyzed by DNA polymerase. The oligonucleotide-primed material is split into four separate reaction tubes. Each tube receives a small amount of an α[32P]-;abelled dNTP whose radioactivity allows the newly synthesized DNA to be visualized by autoradiography.

Next, each tube receives an excess of the four nonradioactive dNTP molecules and a small amount of one of the four ddNTPs. For example, the A reaction tube receives an excess of nonradioactive dTTP, dGTP, dCTP, and dATP mixed with a small amount of ddATP. DNA polymerase is then added to the reaction mixture. As the polymerase replicates the DNA, it occasionally incorporates a ddATP residue instead of a dATP residue, and synthesis of the growing DNA chain is terminated. Random incorporation of ddATP results in the production of newly synthesized DNA fragments of different lengths, each ending with A (i.e., ddA). The length of each fragment corresponds to the distance from the 5′-end of the primer to one of the adenine residues in the sequence.

Adding a different dideoxyribonucleotide to each reaction tube produces a different set of fragments: ddTTP produces fragments that terminate with T, ddGTP with G, and ddCTP with C. The newly synthesized chains from each sequencing reaction are separated from the template DNA.

Finally, the mixtures from each sequencing reaction are subjected to electrophoresis in adjacent lanes on a sequencing gel, where the fragments are resolved by size. The sequence of the DNA molecule can then be read from an autoradiograph of the gel.


This technique has also been modified to allow automation for high throughput applications like genomic sequencing. Instead of using radioactivity automated sequencing relies on fluorescently labeled dideoxynucleotides (four colors, one for each base) to detect the different chain lengths. In this system the gel is “read” by a fluorimeter and the data are stored in a computer file. Additionally, the sequencing machine can also provide a graphic chromatogram that shows the location and size of each fluorescent peak on the gel as they passed the detector.


The bottom figure is from Wikipedia. The other figures and the text are from Horton, H.R., Moran, L.A., Scrimgeour, K.G., Perry, M.D., and Rawn, J.D. (2006) Principles of Biochemistry 4th edition, Pearson Prentice Hall, Upper Saddle River, New Jersey, USA.
© Laurence A. Moran, Pearson Prentice Hall

Atheists Are Smarter than Agnostics

 
Science proves it.


Monday, December 15, 2008

Why Everyone Should Learn the Theory of Evolution

 
Why Everyone Should Learn the Theory of Evolution is the title of an editorial on the Scientific American website.

The editors begin by pointing out that Charles Darwin was a genius who deserves every bit as much recognition as Albert Einstein. I agree 100%. In my opinion Darwin is the greatest scientist who ever lived and it's about time we started to recognize his genius.

The rest of the editorial isn't as good. It's clear that the editors have a myopic view of evolution. They seem to think that the sort of evolution everyone should learn can be found in The Origin of Species.
But Darwin is so much more than just a quaint, Victorian historical figure whose bust in the pantheon deserves a place among those of other scientific greats. Theory needs to explain past, present and future—and Darwin’s does all three in a form that requires no simplifying translation. His theory is readily accessible to any literate person who allots a pleasurable interlude for On the Origin of Species, its prose sometimes bordering on the poetic: “... from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”
Now, you can learn a lot about evolution from reading Darwin's 1859 book. You can learn, for example, about natural selection and you can also learn about the inheritance of acquired characteristics.

You won't learn anything about genetics or biochemistry or developmental biology or bacteria or genomes or whether birds are related to dinosaurs.

The editors link to another article published in this month's Scientific American: The Evolution of Evolution. The article by Gary Stix attempts to explain Darwin's Living Legacy--Evolutionary Theory 150 Years Later. It doesn't do a very good job but at least it raises some interesting questions.
The concept of evolution as a form of branching descent from a common ancestor achieved a relatively rapid acceptance, but accommodation for natural selection came much more slowly, even within the scientific community. The hesitation was understandable. In his work, Darwin had not described a mechanism for inheritance, attributing it to minuscule, hypothetical “gemmules” that ejected from each tissue and traveled to the sex organs, where copies were made and passed to subsequent generations. It took until the decades of the 1930s and 1940s for natural selection to gain broad acceptance.

It was then that the modern synthesis emerged as an expansive framework that reconciled Darwin’s natural selection with the genetics pioneered by Gregor Mendel. In 1959, the centennial of the publication of Origin of Species, the place of natural selection seemed assured.

But in the ensuing years, the scope of evolutionary biology has had to broaden still further to consider such questions as whether the pace of evolution proceeds in fits and starts—a paroxysm of change followed by long periods of stasis. Do random mutations frequently get passed on or disappear without enhancing or diminishing fitness, a process called genetic drift? Is every biological trait an evolutionary adaptation, or are some characteristics just a random by-product of a physical characteristic that provides a survival advantage?

The field has also had to take another look at the notion that altruistic traits could be explained by natural selection taking place across whole groups. And as far as the origin of species, what role does genetic drift play? Moreover, does the fact that single-celled organisms often trade whole sets of genes with one another undermine the very concept of species, defined as the inability of groups of organisms to reproduce with one another? The continued intensity of these debates represents a measure of the vigor of evolutionary biology—as well as a testament to Darwin’s living legacy.
We know the answers to some of these questions. The modern version of evolution is the one that everyone should learn—not the 150-year-old version that Darwin wrote about.

If the editors of Scientific American don't understand the difference then our society is in a lot worse trouble than I imagined.



Monday's Molecule #101

 
This is the last Monday's Molecule for 2008. There will be a short Christmas break. Monday's Molecule will return on January 5th. As part of the Christmas celebrations, this week's molecule is a gift.

Your task is to identify this molecule and give it a biochemically accurate name (the IUPAC name would be perfect). The Nobel Laureate should be obvious once you identify the molecule.

The first one to correctly identify the molecule and name the Nobel Laureate, wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize.

There are four ineligible candidates for this week's reward: Ms. Sandwalk from Mississauga, Ontario, Canada, Alex Ling of the University of Toronto, Timothy Evans of the University of Pennsylvania, and John Bothwell of the Marine Biological Association of the UK in Plymouth, UK. John, Dale and Ms. Sandwalk have offered to donate the free lunch to a deserving undergraduate so the next two undergraduates to win and collect a free lunch can also invite a friend. Alex got the first one.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the "molecule" and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The molecule is 2&prime,3′-dideoxycytidine 5′-monophosphate. This molecule differs from the normal cellular version of deoxycytidine because it is missing a second hydroxyl group at the 3′ position on the sugar. The triphosphate version of this molecule is a substrate for DNA polymerase and it will be incorporated into a growing DNA chain. However, once it is incorporated, the polymerization reaction stops because the 3′ hydroxyl group is essential for addition of the next nucleotide.

Dideoxynucleotides are used in the chain termination method of DNA sequencing developed by Frederick Sanger. Sanger received his second Nobel Prize in 1980 for developing this method, which remains the most popular method of DNA sequencing.

I was surprised that only a few people responded and even more surprised that some of the regulars didn't give a correct name for this molecule. There is no winner this week because I am being strict about nomenclature. If you didn't specify where the phosphate is attached (5′) or you used "cytosine" instead of "cytidine," then you don't get a free lunch! (Cytosine is the base, cytidine is the nucleoside.)


Conservatives Condone Torture, Liberals Don't

 
Let me make this perfectly clear—in my opinion, any society that condones and practices torture is a society in which the rights of all individuals are diminished. The rights of individuals and the goal of a just society are qualitative traits, not quantitative traits. If some people are deprived of those rights and if some people aren't part of the just society, then the "rights" don't exist and the society is not just. You can't have the right to fair treatment under the law in some situations but not in others. That's a mockery of justice.

Reuel Marc Gerecht is a former Central Intelligence Agency officer and a fellow at the Foundation for Defense of Democracies (FDD). The leadership of FDD consists of people like Newt Gingrich, Bill Kristol, Steve Forbes, and Joe Lieberman. They are "small-c" conservatives. Mostly Republicans, I think (including Lieberman, the Republican-in-all-but-name).

Last Saturday Gerecht wrote an opinion piece in The New York Times in defense of torture [Out of Sight].

He starts off by defending extraordinary rendition. This is the tactic of sending suspected criminals to other countries where they can be tortured and then returned to the USA. The idea is to be able to deny that the USA is in violation of its own Constitution and respect for human rights.
Mr. Obama will soon face the same awful choices that confronted George W. Bush and Bill Clinton, and he could well be forced to accept a central feature of their anti-terrorist methods: extraordinary rendition. If the choice is between non-deniable aggressive questioning conducted by Americans and deniable torturous interrogations by foreigners acting on behalf of the United States, it is almost certain that as president Mr. Obama will choose the latter.
Aside from the fact that torture is legally and ethically wrong, there's three other slight problems with this tactic. First, who are they trying to deceive? Is there anyone with an IQ over 50 that can be fooled by extraordinary rendition?1 Second, there's very little evidence that torture works. Third, many innocent people have been tortured.

Canada is particularly sensitive about rendition because of Maher Arar. Arar, a Canadian citizen, was arrested in 2002 at Kennedy Airport in New York and send to Syria where he was tortured and confined for 10 months. He was subsequently released and the Canadian government has established that he is innocent [Canadian cleared of terrorism after rendition, torture in Syria].

We don't know how many other innocent people have been tortured but chances are the numbers are substantial. The problem with rendition is that the individuals are deprived of their right to face their accusers and prove their innocence. No respectable society should condone such behavior.

Gerecht then raises the standard canard that seems to be the last refuge of those who would violate people's rights.
However, troubles in Pakistan may well reverse Mr. Obama’s luck. He has said he intends to be hawkish about fighting Al Qaeda and the Taliban in Central Asia. So, let us suppose that he increases the number of Special Forces raids into Pakistan, and those soldiers capture members of Al Qaeda and their computers, and learn that the group has advanced plans for striking American and European targets, but we don’t know specifically where or when.

What would Mr. Obama do? After all, if we’d gotten our hands on a senior member of Al Qaeda before 9/11, and knew that an attack likely to kill thousands of Americans was imminent, wouldn’t waterboarding, or taking advantage of the skills of our Jordanian friends, have been the sensible, moral thing to do with a holy warrior who didn’t fear death but might have feared pain?
No, Mr. Gerecht, torture is not a sensible, moral thing to do. It is stupid and immoral.

Stupid because the chances of finding out useful information under such circumstances are slim to zip. Stupid because under the Golden Rule we are putting the lives of all of our citizens at risk when they are captured by the bad guys. Stupid because it is contrary to the very thing that we are supposed to be fighting for. Stupid because the Americans who carry out rendition can be, and should be, put in jail. (I would even advocate that those who advocate breaking the law as almost as guilty.)

Immoral because .... never mind, he wouldn't know morality if it bit him on the posterior.

This issue is important in Canada for another reason. Our recently appointed Liberal leader, Michael Ignatieff, has a somewhat checkered history of modest support for torture. Recently his writings have been more clear about his opposition to torture while pointing out the moral dilemma [If torture works ...]. I'm going to quote extensively from his essay because this is a man who will be Prime Minister of Canada.
It is difficult to think about torture honestly. In a recent article on the interrogation techniques employed by the US, the writer Mark Bowden observed that few "moral imperatives make such sense on a large scale, but break down so dramatically in the particular." The moral imperative—do not torture, any time, anywhere, in any circumstances—is mandated by the UN convention against torture and other cruel, inhuman or degrading treatment or punishment. "No exceptional circumstances whatsoever, whether a state of war or a threat of war, internal political instability or any other public emergency," says the convention, can "be invoked as a justification of torture." That terrorists themselves torture does not change these imperatives. Our compliance does not depend on reciprocity.

.....

Elshtain justifies coercive interrogation using a complex moral calculus of "dirty hands": good consequences cannot justify bad acts, but bad acts are sometimes tragically necessary. The acts remain bad, and the person must accept the moral opprobrium and not seek to excuse the inexcusable with the justifications of necessity.

My own work on "lesser evils" brings me close to the Elshtain position. I agree with her that necessity may require the commission of bad acts, which necessity, nevertheless, cannot absolve of their morally problematic character—but I still have a problem. If one enumerates the forms of coercive interrogation that have been judged to be inhuman and degrading by the Israeli and the European courts—hooding, holding subjects in painful positions, exposing them to cold or heat or ear-splitting noise—these techniques also seem unacceptable, though at a lower threshold of awfulness, than torture. Like Elshtain, I am willing to get my hands dirty, but unlike her, I have practical difficulty enumerating a list of coercive techniques that I would be willing to have a democratic society inflict in my name. I accept, for example, that a slap is not the same thing as a beating, but I still don't want interrogators to slap detainees because I cannot see how to prevent the occasional slap deteriorating into a regular practice of beating. The issue is not, as Elshtain implies, that I care overmuch about my own moral purity but rather that I cannot see any clear way to manage coercive interrogation institutionally so that it does not degenerate into torture.

So I end up supporting an absolute and unconditional ban on both torture and those forms of coercive interrogation that involve stress and duress, and I believe that enforcement of such a ban should be up to the military justice system plus the federal courts. I also believe that the training of interrogators can be improved by executive order and that the training must rigorously exclude stress and duress methods.

Two significant problems remain. First of all, there is the problem of the exceptional case, one where lives can be saved by the application of physical methods that amount to torture. "Ticking bomb cases" cannot be wished away. They might arise especially where an American or European city faced the threat of WMD. An outright ban on torture and coercive interrogation leave a conscientious security officer with little choice but to disobey the ban. In this event, as the Israeli supreme court has said, even a conscientious agent acting in good faith to save lives should be charged with a criminal offence and be required to stand trial. At trial, a defence of necessity could be entered in mitigation of sentence, but not to absolve or acquit. This is the only solution I can see that remains consistent with an absolute ban on torture and coercive interrogation. Let us not pretend that the enforcement of this rule would be easy. Where the threat could be shown to be genuine, it seems evident that few legal systems would punish such a conscientious offender. So an outright ban on torture creates the problem of the conscientious offender. This is a small price to pay for a ban on torture.

Does an outright ban on torture and coercive interrogation meet the test of realism? Would an absolute ban on torture and coercive interrogation using stress and duress so diminish the effectiveness of our intelligence-gathering that it would diminish public safety? It is often said—and I argued so myself—that neither coercive interrogation nor torture is necessary, since entirely lawful interrogation can secure just as effective results. There must be some truth to this. Israeli interrogators have given interviews assuring the Israeli public that physical duress is unnecessary. But we are grasping at straws if we think this is the entire truth. As Posner and others have tartly pointed out, if torture and coercion are both as useless as critics pretend, why are they used so much? While some abuse and outright torture can be attributed to individual sadism, poor supervision and so on, it must be the case that other acts of torture occur because interrogators believe, in good faith, that torture is the only way to extract information in a timely fashion. It must also be the case that if experienced interrogators come to this conclusion, they do so on the basis of experience. The argument that torture and coercion do not work is contradicted by the dire frequency with which both practices occur. I submit that we would not be "waterboarding" Khalid Sheikh Mohammed—immersing him in water until he experiences the torment of nearly drowning—if our intelligence operatives did not believe it was necessary to crack open the al Qaeda network that he commanded. Indeed, Mark Bowden points to a Time report in March 2003 that Sheikh Mohammed had "given US interrogators the names and descriptions of about a dozen key al Qaeda operatives believed to be plotting terrorist attacks." We must at least entertain the possibility that the operatives working on Sheikh Mohammed in our name are engaging not in gratuitous sadism but in the genuine belief that this form of torture—and it does qualify as such—makes all the difference.

If they are right, then those who support an absolute ban on torture had better be honest enough to admit that moral prohibition comes at a price. It is possible, at least in theory, that subjecting interrogators to rules that outlaw torture and coercive interrogation, backed up by punishment if they go too far, will create an interrogation regime that allows some interrogation subjects to resist divulging information and prevents our intelligence services from timely access to information that may save lives.

If there is a significant cost to an outright ban on coercive interrogation and torture, what can possibly justify it? Many of the arguments that human rights activists make in justification amount to the claim that torture shames their moral identity as human beings and as citizens, and that they do not wish such acts to be committed in their names. Other citizens in a democracy may not value their own moral scruple over the collective interest in having accurate security information, even if collected by dubious means. It may be obvious to human rights activists how to adjudicate these claims, but it is not obvious to me. That is, I do not see any trumping argument on behalf of the rights and dignity of security detainees that makes their claims prevail over the security interests (and human right to life) of the majority. The best I can do is to relate the ban on torture to the political identity of the democracies we are trying to defend—by claiming that democracies limit the powers that governments can justly exercise over the human beings under their power, and that these limits include an absolute ban on subjecting individuals to forms of pain that strip them of their dignity, identity and even sanity.

We cannot torture, in other words, because of who we are. This is the best I can do, but those of us who believe this had better admit that many of our fellow citizens are bound to disagree. It is in the nature of democracy itself that fellow citizens will define their identity in ways that privilege security over liberty and thus reluctantly endorse torture in their name. If we are against torture, we are committed to arguing with our fellow citizens, not treating those who defend torture as moral monsters. Those of us who oppose torture should also be honest enough to admit that we may have to pay a price for our own convictions. Ex ante, of course, I cannot tell how high this price might be. Ex post—following another terrorist attack that might have been prevented through the exercise of coercive interrogation—the price of my scruple might simply seem too high. This is a risk I am prepared to take, but frankly, a majority of fellow citizens is unlikely to concur.
I'm more skeptical than Ignatieff about the efficacy of torture. Just because lots of people do it does not sound like a good argument for defending the usefulness of torture.

Nevertheless, when it comes to the bottom line, I'm with Michael Ignatieff, "We cannot torture ... because of who we are." If there's a price to be paid for doing the right thing then I'm prepared to pay it and suffer the consequences.


1. Apparently patriotic conservatives are easily fooled—that's why I set the cutoff IQ so high.

[Hat Tip: daimnation! via Canadian Cynic]

Sunday, December 14, 2008

Women of The View Discuss Evolution

 
PZ Myers posted this on Pharyngula but in case some of you haven't seen it there, I though I'd post it too.

I find it really shocking that people would talk like this on television knowing that they're being watched by millions of people. Surely they realize that what they're saying conflicts with the consensus among scientific experts? I can understand how they might justify their anti-science position in their own minds in the privacy of their church or home but in public?

They must have a very low opinion of scientists.



Scientific American: The Evolution of Evolution

 
The latest edition of Scientific American is all about "The Evolution of Evolution."

Here's how the editor-in-chief, John Rennie introduces the articles.
When Charles Darwin published "On the Origin of Species" in 1859, he touched off a Cambrian explosion in evolutionary thought. Naturalists had theorized about evolution for centuries before him, but their ideas were generally unfruitful, untestable or wrong. Darwin's breakthrough insight was not that a simple mechanism—natural selection—made evolution possible. Rather it was that in organisms whose environments changed nonrandomly and whose reproductive success in that environment depended on inherited traits, evolution became inevitable.

In the decades that followed, Darwin's ideas connected up with the nascent field of genetics and then, at an ever quickening pace, with molecular biology, ecology and embryology. The explanatory power his concepts proved irresistible. Today 200 years after his birth and 150 years after "Origin of Species," Darwin's legacy is a larger, richer, more diverse set of theories than he could have imagined.
You will enjoy reading the articles to see exactly what Scientific American means when they talk of a "richer, more diverse set of theories." Here's the list.

SciAm Perspectives: A Theory for Everyman
; by The Editors; 1 Page
Evolution should be taught as a practical tool for understanding drug resistance and the price of fish.
Darwin's Living Legacy; by Gary Stix; 6 Pages
A Victorian amateur undertook a lifetime pursuit of slow, meticulous observation and thought about the natural world, producing a theory 150 years ago that still drives the contemporary scientific agenda.
Testing Natural Selection; by H. Allen Orr; 8 Pages
Biologists working with the most sophisticated genetic tools are demonstrating that natural selection plays a greater role in the evolution of genes than even most evolutionists had thought.
From Atoms to Traits; by David M. Kingsley; 8 Pages
Charles Darwin saw that random variations in organisms provide fodder for evolution. Modern scientists are revealing how that diversity arises from changes to DNA and can add up to complex creatures or even cultures.
The Human Pedigree; by Kate Wong; 4 Pages
Some 180 years after unearthing the first human fossil, paleontologists have amassed a formidable record of our forebears.
This Old Body; by Neil H. Shubin; 4 Pages
Evolutionary hand-me-downs inherited from fish and tadpoles have left us with hernias, hiccups and other maladies.
What Will Become of Homo sapiens?; by Peter Ward; 6 Pages
Contrary to popular belief, humans continue to evolve. Our bodies and brains are not the same as our ancestors’ were—or as our descendants’ will be.
Four Fallacies of Pop Evolutionary Psychology; by David J. Buller; 8 Pages
Some evolutionary psychologists have made widely popularized claims about how the human mind evolved, but other scholars argue that the grand claims lack solid evidence.
Evolution in the Everyday World; by David P. Mindell; 8 Pages
Understanding of evolution is fostering powerful technologies for health care, law enforcement, ecology, and all manner of optimization and design problems.
The Science of Spore; by Ed Regis; 2 Pages
A computer game illustrates the difference between building your own simulated creature and real-life natural selection.
The Latest Face of Creationism; by Glenn Branch and Eugenie C. Scott; 8 Pages
Creationists who want religious ideas taught as scientific fact in public schools continue to adapt to courtroom defeats by hiding their true aims under ever changing guises.


Gene Genie #41

 
The 41th edition of Gene Genie has been posted at ScienceRoll [Gene Genie #41: Carnivalome].
Gene Genie is the blog carnival of clinical genetics and personalized medicine. I’ve received more than 25 submissions for this edition which is dedicated to the human genome and videos in clinical genetics.
The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....
  1. Scienceroll
  2. Sciencesque
  3. Genetics and Health
  4. Sandwalk
  5. Neurophilosophy
  6. Scienceroll
  7. Gene Sherpa
  8. Eye on DNA
  9. DNA Direct Talk
  10. Genomicron
  11. Med Journal Watch
  12. My Biotech Life
  13. The Genetic Genealogist
  14. MicrobiologyBytes
  15. Cancer Genetics
  16. Neurophilosophy
  17. The Gene Sherpa
  18. Eye on DNA
  19. Scienceroll
  20. Bitesize Bio
  21. BabyLab
  22. Sandwalk
  23. Scienceroll
  24. biomarker-driven mental health 2.0
  25. The Gene Sherpa
  26. Sciencebase
  27. DNA Direct Talk
  28. Greg Laden’s Blog
  29. My Biotech Life
  30. Gene Expression
  31. Adaptive Complexity
  32. Highlight Health
  33. Neurophilosophy
  34. ScienceRoll
  35. Microbiology Bytes
  36. Human Genetic Disordrs
  37. The Genetic Genealogist
  38. ScienceRoll
  39. Genetics & Health
  40. Human Genetics Disorders
  41. ScienceRoll


Saturday, December 13, 2008

Epigenetics at SEED

Epigenetics is one of the latest fads in biology. It arises out of evo-devo and its proponents tell us that epigenetics will transform the way we think about evolution. I've been trying to understand this phenomenon starting with some simple questions about what, exactly, is so new. I'd be happy if someone could just explain what they mean by "epigenetics" [Epigenetics in New Scientist, Epigenetics Revisited, Epigenetics, Epigenetics Again].

Eva Jablonka is a Professor at the Cohn Institute for the History and Philosophy of Science and Ideas at Tel-Aviv University (Israel). Jablonka was one of the 16 people who met in Alterberg, Austria last summer to discuss the faults in modern evolutionary biology. She writes an article entitled "Extending Darwinism" in the latest issue of SEED magazine.
I and several other biologists believe the MS [Modern Synthesis1] is in need of serious revision. Growing evidence indicated that there is more to heredity than DNA, that heritable non-DNA variations can take place during development, sometimes in response to an organism's environment. The notion of soft inheritance is returning to reputable scientific inquiry. Moreover, there seem to be cellular mechanisms activated during periods of extreme stress that trigger bursts of genetic and non-genetic heritable variations, inducing rapid evolutionary change. These realizations promise to profoundly alter our view of evolutionary dynamics.
Nothing new here, folks. It's just the same old gibberish that we've been hearing for the past several years.

If there is as much natural variation induced by environmental factors as lab studies suggest, then rapid evolutionary change could occur without any genetic change at all.

Eva Jablonka
But there is one thing that's worth noting. Eva Jablonka has done what few of her fellow epigeneticists have attempted. She defines what she means by epigenetics!
Epigenetics is a term that includes all the processes underlying developmental flexibility and stability, and epigenetic inheritance is part of this. Epigenetic inheritance is the transmission of developmental variations that have nothing to do with changes in the DNA base sequences. In its broad sense, it covers the transmission of any differences that do not depend on gene differences, so it encompasses the cultural inheritance of different religious beliefs in humans and song dialects in birds. It even includes the developmental legacies that a young mammal may receive from its mother through her placenta or milk—transmitted antibodies, for example, or chemical traces that tell the youngsters what the mother has been eating and, therefore, what they should eat.
Yes, but does it include the kitchen sink?

The good thing about incorporating these things into evolutionary theory is that it solves the problem of creationism. As long as creationism is passed on from parent to child then it becomes part of evolution. Isn't that cool?


1. Her version of the Modern Synthesis only includes natural selection.

A Holy Alliance?

 
Mario Beauregard is an Associate Researcher in the Departments of Radiology and Psychology at the University of Montreal in Montreal, Quebce, Canada. He is best known as the co-author of The Spiritual Brain with Denyse O'Leary.

Jeffrey M. Schwartz is a research psychiatrist at the School of Medicine at the University of California at Los Angeles (USA). He signed the Discovery Institute's "Scientific Dissent from Darwinism" statement.

Beauregard and Schwartz joined in a holy alliance to write a letter of protest to New Scientist concerning an article published a few months ago. The article was critical of people like Beauregard and Schwartz who mix religion and science.
Your writer's attempt to smear scientists who are looking for new directions, while perhaps entertaining, is a poor substitute for thoughtful coverage of a growing area.
Perhaps we should be looking to writers like Denyse O'Leary for thoughtful coverage?


The Problem with Microarrays

 
From The Endeavour by John D. Cook: Why microarray study conclusions are so often wrong and from Reproducible Results: Three reasons to distrust microarray results


[Hat Tip: A Blog Around the Clock]

Does Your Heart Bleed for Jodi?

 
Times are tough these days. People have lost their jobs and many are struggling to put food on the table and keep a roof over their heads. Christmas is not going to be a happy time in many households across North America.

The New York Times, bless its heart, is not unaware of what's going on. Lisa Foderaro has written an article that's sure to bring a tear to your eye as she documents the devastating effect of job loss on the life of a teenager [As the Rich Get Poorer, Teenagers Feel the Crunch ].
Jodi Hamilton began her senior year of high school in Woodcliff Lake, N.J., this fall on the usual prosperous footing. Her parents were providing a weekly allowance of $100 and paying for private Pilates classes, as well as a physics tutor who reported once a week to their 4,000-square-foot home.

But in October, Jodi’s mother lost her job managing a huge dental practice in the Bronx, then landed one closer to home that requires more hours for less money. Pilates was dropped, along with takeout sushi dinners, and Jodi’s allowance, which covers lunch during the week, slipped to $60. Instead of having a tutor, Jodi has become a tutor, earning $150 a week through that and baby-sitting.

“I just thought it would be responsible to get a job and have my own money so my parents didn’t have to pay for everything,” said Jodi, who is 17. “I always like to be saving up for something that I have my eye on — a ring, a necklace, a handbag.”
Later on in the article we hear about some other teenagers who have been forced to find a job.
Teenagers from working- and middle-class families are, of course, feeling similar — if not more acute — pressure. Sumit Pal, 17, a senior at Information Technology High School in Queens, said his parents cut his $5 weekly allowance two months ago after the deli where his father works started to lose business. Sumit was interviewed two weeks ago for a job at a company that sponsors rock bands.

“I don’t mind losing my allowance,” he said. “It goes toward other things, like groceries.”
How nice of Ms. Foderaro to mention that the lower classes are also, "of course," feeling the pinch.


[Hat Tip: Canadian Cynic pointed to this posting on The Vanity Press: Pitchforks and Torches Time]

Friday, December 12, 2008

What Is the Scientific Method?

 

There are lots of interesting things in this month's issue of SEED magazine. One of them is a survey of scientists in the USA, UK, France and Germany.

SEED magazine conducted a survey where it asked the following question of 1000 scientists in the USA, UK, France, and Germany: "Does the scientific method describe how you do science?" [SEED: State of Science].

81% said "yes."

I would answer "no" but my answer depends very much on what I think the question means. I think it's fair to use the common understanding of the "scientific method," the one that's taught in fifth grade.

Here's the simple version that's described on the Wikipedia site [Scientific Method].
  1. Use your experience: Consider the problem and try to make sense of it. Look for previous explanations. If this is a new problem to you, then move to step 2.
  2. Form a conjecture: When nothing else is yet known, try to state an explanation, to someone else, or to your notebook.
  3. Deduce a prediction from that explanation: If you assume 2 is true, what consequences follow?
  4. Test : Look for the opposite of each consequence in order to disprove 2. It is a logical error to seek 3 directly as proof of 2. This error is called affirming the consequent.
Is this what most people think about when they hear the term "scientific method"?

If you are a scientist, how would you have answered the SEED question and what definition of "scientific method" do you have in mind?


Religious Scientists

 
There are lots of interesting things in this month's issue of SEED magazine. One of them is a survey of scientists in the USA, UK, France and Germany.

SEED asked a total of 1000 scientists whether they were "atheist or agnostic," "practicing nonbelievers," "believers," or "spiritual" [SEED: State of Science].

Here's the result, in percent, for each of the four choices.

USA: atheist = 17%, nonbelievers = 6%, believers = 53%, spiritual = 24%
UK: atheist = 44%, nonbelievers = 10%, believers = 35%, spiritual = 11%
France: atheist = 50%, nonbelievers = 6%, believers = 39%, spiritual = 5%
Germany: atheist = 40%, nonbelievers = 24%, believers = 32%, spiritual = 4%

I find this surprising. The distribution isn't that much different from the general public in each of the countries. I was under the impression that scientists are considerably less religious than the society in which they live.

Perhaps this is because the SEED definition of scientist is more flexible than the one I would use. Here's the breakdown of their survey group.

Social Science: 24%
Medicine: 23%
Life Sciences: 15%
Engineering: 12%
Physical Sciences: 9%
Computer Science: 9%
Mathematics: 8%


Richard Cizik Resigns

 
Most of you have never heard of Richard Cizik. Let me explain why his resignation is important.

A few days ago I posted an opinion on framing and referred you to Matt Nisbet who claims that Richard Cizik is a good example of how to present science to the general public. Cizik is Vice President for governmental affairs of the National Association of Evangelicals (NAE). Nisbet thinks he is the top climate communicator [see Communicating the Truth about Climate Change].

I quoted from Nisbet's blog where he refers approvingly to a Cizik interview with Terry Gross.

Yesterday Christianity Today announced that Richard Cizik has been forced to resign his position in the National Association of Evangelicals [Richard Cizik Resigns from the National Association of Evangelicals]
Richard Cizik resigned Wednesday night as vice president for governmental affairs of the National Association of Evangelicals (NAE) during a week of growing uproar over his comments that he is shifting his views on same-sex unions.

"Although he has subsequently expressed regret, apologized, and affirmed our values, there is a loss of trust in his credibility as a spokesperson among leaders and constituencies," Leith Anderson, president of the NAE wrote to board members today. Cizik did not return calls for comment.

Last year, more than two dozen evangelical leaders sought to oust Cizik, who has been vice president for 28 years, because of his "relentless campaign" on global warming.

"For better or for worse, Rich became a great, polarizing figure," said Charles Colson of Prison Fellowship. "He was gradually, over a period of time, separating himself from the mainstream of evangelical belief and conviction. So I'm not surprised. I'm sorry for him, but I'm not disappointed for the evangelical movement."

Cizik spoke mostly on the environment in a December 2 interview with Terry Gross on National Public Radio's Fresh Air, but he made brief remarks about same-sex civil unions, gay marriage, and his early support of President-elect Barack Obama.

In a short portion of the program, Gross asked him, "A couple of years ago when you were on our show, I asked you if you were changing your mind on that. And two years ago, you said you were still opposed to gay marriage. But now as you identify more with younger voters, would you say you have changed on gay marriage?"

Cizik responded, "I'm shifting, I have to admit. In other words, I would willingly say that I believe in civil unions. I don't officially support redefining marriage from its traditional definition, I don't think."
I wonder if Matt still thinks that Richard Cizik is the best example of successful framing?


[Hat Tip: Friendly Atheist: Christian Leader Resigns Because of His Almost-Tolerant Views of Homosexuals]

Thursday, December 11, 2008

Noah's Ark

 
Yesterday I dropped a hint about a plastic model of Noah's Ark. I suggested it might make a good gift ... in case anyone was thinking about gifts.

Ms. Sandwalk was a bit insulted 'cause we already have a perfectly good ark that she made—complete with animals. Here's a photo of her work. I have to admit that it's a lot better than the plastic model.




Matt Nisbet Explains His Anti-Dawkins Spin

 
Here's Mat Nisbet explaining why Richard Dawkins is such an evil person. In the second part of this video he tries to explain why scientists don't like Matt Nisbet very much.

The most interesting question is near the end of the video when he states that no one would ever criticize the National Academies for misrepresenting science in order to make it seem compatible with religion. He knows that this is not true (e.g., An Example of Framing by Matt Nisbet). We have a word for people who delberately say things they know to be untrue ... it's called framing.





Belief in Astrology Falls to Second Last Place!

 
According to the latest Harris Poll only 31% of Americans believe in astrology and only 24% believe that they were once another person.

Other interesting facts are that a substantial majority of Americans believe in multiple supernatural beings (polytheism). Besides the regular God, they believe in angels and the devil.

 Believe InDon't
Believe In
Not Sure
     %    %    %
God   80   10   9
Miracles   75   14   12
Heaven   73   14   13
Jesus is God or the Son of God   71   17   12
Angels   71   17   12
The resurrection of Jesus Christ   70   18   13
Survival of the soul after death   68   15   17
Hell   62   24   13
The Virgin birth   61   24   15
The devil   59   27   14
Darwin’s theory of evolution   47   32   22
Ghosts   44   39   17
Creationism   40   31   29
UFOs   36   39   25
Witches   31   54   14
Astrology   31   51   18
Reincarnation–that you were once another person   24   53   23

In other news, 37% believe that the Old Testament is the word of God but only 14% believe The Torah is the word of God.

15% say they are not at all religious and 10% don't beleive in God.


Denyse O'Leary Loses!

 
The results are in and Denyse O'Leary's blog Post-Darwinist did not win in the Best Canadian Sci/Tech category. Here are the final results from Best Sci/Tech Blog of 2008.
  1. Sync, the Tech & Gadgets Blog 108 votes 35.29%
  2. Synchro Blogue 87 votes 28.43%
  3. DeSmogBlog 56 votes 18.3%
  4. Post Darwinist 31 votes 10.13%
  5. Dusan Writer 24 votes 7.84%
Bill Dembski demonstrates that he has been following the vote very closely. He also demonstrates why he is so good at math [Reinstating the Explanatory Filter].
P.S. Congrats to Denyse O’Leary, whose Post-Darwinist blog tied for third in the science and technology category from the Canadian Blog Awards.


Universal Declaration of Human Rights

 
Yesterday was the 60th anniversary of the signing of the Universal Declaration of Human Rights. It was adopted on December 10, 1948 by the General Assembly of the United Nations. Most of the current members of the United Nations ignore the majority of articles in the Universal Declaration of Human Rights yet they are allowed to remain members of the United Nations.

PREAMBLE

Whereas recognition of the inherent dignity and of the equal and inalienable rights of all members of the human family is the foundation of freedom, justice and peace in the world,

Whereas disregard and contempt for human rights have resulted in barbarous acts which have outraged the conscience of mankind, and the advent of a world in which human beings shall enjoy freedom of speech and belief and freedom from fear and want has been proclaimed as the highest aspiration of the common people,

Whereas it is essential, if man is not to be compelled to have recourse, as a last resort, to rebellion against tyranny and oppression, that human rights should be protected by the rule of law,

Whereas it is essential to promote the development of friendly relations between nations,

Whereas the peoples of the United Nations have in the Charter reaffirmed their faith in fundamental human rights, in the dignity and worth of the human person and in the equal rights of men and women and have determined to promote social progress and better standards of life in larger freedom,

Whereas Member States have pledged themselves to achieve, in co-operation with the United Nations, the promotion of universal respect for and observance of human rights and fundamental freedoms,

Whereas a common understanding of these rights and freedoms is of the greatest importance for the full realization of this pledge,

Now, Therefore THE GENERAL ASSEMBLY proclaims THIS UNIVERSAL DECLARATION OF HUMAN RIGHTS as a common standard of achievement for all peoples and all nations, to the end that every individual and every organ of society, keeping this Declaration constantly in mind, shall strive by teaching and education to promote respect for these rights and freedoms and by progressive measures, national and international, to secure their universal and effective recognition and observance, both among the peoples of Member States themselves and among the peoples of territories under their jurisdiction.

Article 1.

All human beings are born free and equal in dignity and rights.They are endowed with reason and conscience and should act towards one another in a spirit of brotherhood.

Article 2.

Everyone is entitled to all the rights and freedoms set forth in this Declaration, without distinction of any kind, such as race, colour, sex, language, religion, political or other opinion, national or social origin, property, birth or other status. Furthermore, no distinction shall be made on the basis of the political, jurisdictional or international status of the country or territory to which a person belongs, whether it be independent, trust, non-self-governing or under any other limitation of sovereignty.

Article 3.

Everyone has the right to life, liberty and security of person.

Article 4.

No one shall be held in slavery or servitude; slavery and the slave trade shall be prohibited in all their forms.

Article 5.

No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment.

Article 6.


Everyone has the right to recognition everywhere as a person before the law.

Article 7.

All are equal before the law and are entitled without any discrimination to equal protection of the law. All are entitled to equal protection against any discrimination in violation of this Declaration and against any incitement to such discrimination.

Article 8.

Everyone has the right to an effective remedy by the competent national tribunals for acts violating the fundamental rights granted him by the constitution or by law.

Article 9.

No one shall be subjected to arbitrary arrest, detention or exile.

Article 10.

Everyone is entitled in full equality to a fair and public hearing by an independent and impartial tribunal, in the determination of his rights and obligations and of any criminal charge against him.

Article 11.

(1) Everyone charged with a penal offence has the right to be presumed innocent until proved guilty according to law in a public trial at which he has had all the guarantees necessary for his defence.

(2) No one shall be held guilty of any penal offence on account of any act or omission which did not constitute a penal offence, under national or international law, at the time when it was committed. Nor shall a heavier penalty be imposed than the one that was applicable at the time the penal offence was committed.

Article 12.

No one shall be subjected to arbitrary interference with his privacy, family, home or correspondence, nor to attacks upon his honour and reputation. Everyone has the right to the protection of the law against such interference or attacks.

Article 13.

(1) Everyone has the right to freedom of movement and residence within the borders of each state.

(2) Everyone has the right to leave any country, including his own, and to return to his country.

Article 14.

(1) Everyone has the right to seek and to enjoy in other countries asylum from persecution.

(2) This right may not be invoked in the case of prosecutions genuinely arising from non-political crimes or from acts contrary to the purposes and principles of the United Nations.

Article 15.

(1) Everyone has the right to a nationality.

(2) No one shall be arbitrarily deprived of his nationality nor denied the right to change his nationality.

Article 16.

(1) Men and women of full age, without any limitation due to race, nationality or religion, have the right to marry and to found a family. They are entitled to equal rights as to marriage, during marriage and at its dissolution.

(2) Marriage shall be entered into only with the free and full consent of the intending spouses.

(3) The family is the natural and fundamental group unit of society and is entitled to protection by society and the State.

Article 17.

(1) Everyone has the right to own property alone as well as in association with others.

(2) No one shall be arbitrarily deprived of his property.

Article 18.

Everyone has the right to freedom of thought, conscience and religion; this right includes freedom to change his religion or belief, and freedom, either alone or in community with others and in public or private, to manifest his religion or belief in teaching, practice, worship and observance.

Article 19.

Everyone has the right to freedom of opinion and expression; this right includes freedom to hold opinions without interference and to seek, receive and impart information and ideas through any media and regardless of frontiers.

Article 20.

(1) Everyone has the right to freedom of peaceful assembly and association.

(2) No one may be compelled to belong to an association.

Article 21.

(1) Everyone has the right to take part in the government of his country, directly or through freely chosen representatives.

(2) Everyone has the right of equal access to public service in his country.

(3) The will of the people shall be the basis of the authority of government; this will shall be expressed in periodic and genuine elections which shall be by universal and equal suffrage and shall be held by secret vote or by equivalent free voting procedures.

Article 22.

Everyone, as a member of society, has the right to social security and is entitled to realization, through national effort and international co-operation and in accordance with the organization and resources of each State, of the economic, social and cultural rights indispensable for his dignity and the free development of his personality.

Article 23.

(1) Everyone has the right to work, to free choice of employment, to just and favourable conditions of work and to protection against unemployment.

(2) Everyone, without any discrimination, has the right to equal pay for equal work.

(3) Everyone who works has the right to just and favourable remuneration ensuring for himself and his family an existence worthy of human dignity, and supplemented, if necessary, by other means of social protection.

(4) Everyone has the right to form and to join trade unions for the protection of his interests.

Article 24.

Everyone has the right to rest and leisure, including reasonable limitation of working hours and periodic holidays with pay.

Article 25.

(1) Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control.

(2) Motherhood and childhood are entitled to special care and assistance. All children, whether born in or out of wedlock, shall enjoy the same social protection.

Article 26.

(1) Everyone has the right to education. Education shall be free, at least in the elementary and fundamental stages. Elementary education shall be compulsory. Technical and professional education shall be made generally available and higher education shall be equally accessible to all on the basis of merit.

(2) Education shall be directed to the full development of the human personality and to the strengthening of respect for human rights and fundamental freedoms. It shall promote understanding, tolerance and friendship among all nations, racial or religious groups, and shall further the activities of the United Nations for the maintenance of peace.

(3) Parents have a prior right to choose the kind of education that shall be given to their children.

Article 27.

(1) Everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits.

(2) Everyone has the right to the protection of the moral and material interests resulting from any scientific, literary or artistic production of which he is the author.

Article 28.

Everyone is entitled to a social and international order in which the rights and freedoms set forth in this Declaration can be fully realized.

Article 29.

(1) Everyone has duties to the community in which alone the free and full development of his personality is possible.

(2) In the exercise of his rights and freedoms, everyone shall be subject only to such limitations as are determined by law solely for the purpose of securing due recognition and respect for the rights and freedoms of others and of meeting the just requirements of morality, public order and the general welfare in a democratic society.

(3) These rights and freedoms may in no case be exercised contrary to the purposes and principles of the United Nations.

Article 30.

Nothing in this Declaration may be interpreted as implying for any State, group or person any right to engage in any activity or to perform any act aimed at the destruction of any of the rights and freedoms set forth herein.



A Lesson in How Parliamentary Government Works in Canada

 
Stephen Harper explains how the parliamentary system of government works in Canada.



[Hat Tip: Canadian Cynic who notes that "sometimes this job [mocking Conservatives] is way too easy."

Wednesday, December 10, 2008

Succinate Dehydrogenase

The proper name for succinate dehydrogenase is succinate:quinone oxidoreductase (EC 1,3,5,1). It catalyzes the following reaction,


This is an oxidation-reduction reaction where succinate is oxidized and ubiquinone (Q) is reduced to ubiquinol (QH2). In bacteria the quinone might be menaquinone.

The reaction is part of the citric acid cycle and it is also part of the membrane-associated electron transport system that couples oxidation-reduction reactions to the transfer of protons across a membrane. The resulting protonmotive force is used to drive the synthesis of ATP.

Each year I challenge my students to find a website that correctly depicts the reactions of the citric acid cycle. This year I issued the same challenge to Sandwalk readers: Biochemistry on the Web: The Citric Acid Cycle. Nobody could find a correct version except for a few websites that copied it from my textbook.

The succinate dehydrogenase reaction is one of the reactions that everyone gets wrong. It's incorrect on almost all websites, class powerpoint slides, and also in most biochemistry textbooks. The standard error is to describe the reaction as ....

succinate + FAD → fumarate + FADH2


Let's see how the enzyme works so we can understand why that reaction is incorrect.

The structure of the E. coli enzyme is shown on the right [PDB 1NEK]. There are two polypeptide chains (subunits) making up the head portion of the enzyme at the bottom of the figure. The genes for these polypeptides are present in all species and they are well-conserved. There are one or two membrane-associated subunits (top) and these can differ from species to species.

An FAD coenzyme is covalently bound to the head region of the enzyme. This is the site where succinate is oxidized to fumarate and it projects into the cytoplasm of bacterial cells or the mitochondrial matrix in eukaryotic cells. (Succinate dehdrogenase is a mitochondrial membrane protein.)

Electrons are passed sequentially to three iron-sulfur (Fe-S) clusters and then to quinone. (The reduced form, quinol or QH2, is shown in the structure.) Most versions of succinate dehydrogenase contain a heme b group in the membrane bound portion of the molecule. It's role is unclear. (See Succcinate Dehydrogenase and Evolution by Accident.)

Here's a schematic drawing of the oxidation-reduction reaction (right). The important point is that FAD is part of a short electron transfer chain from succinate to QH2. FADH2 can't be a product of the reaction because it never dissociates from the enzyme. The product is QH2, which can diffuse in the membrane to complex III where it is oxidized.

There are dozens of enzymes that have similar internal electron transfer chains involving FAD or FMN. One of them, α-ketoglutarate deydrogenase is part of the citric acid cycle and another (complex I) is part of the membrane-associated electron transport chain. In these cases the products of the reaction are NADH2 and NAD+. You never see flavin coenzyme listed as a product because it is a transient intermediate that never dissociates from the enzyme.

Succinate deydrogenase is the only example where there is confusion about the real product of the reaction. It's not clear why. Perhaps it's an historical anomaly dating back to the time forty years ago when the real product (QH2) was unknown. That's not a very good excuse for getting it wrong in 2008.

There's one other interesting feature of this enzyme that's worth mentioning. Note that the reduction of Q is accompanied by the uptake of two protons (H+) from the cytoplasmic side of the membrane. This is very important since these protons will eventually be released on the other side of the membrane in the next reaction. This contributes to the formation of a proton gradient across the membrane. (See Ubiquinone and the Proton Pump.)

Access to the active site of quinone reduction is restricted to a small channel that opens into the cytoplasmic side of the membrane. Cheng et al. (2008) have identified a proton wire that leads from the cytoplasm to the quinone. A proton wire is a chain of protons—they are shown as red balls in the figure below. The opening to the cytoplasm is in the middle of this mirror-image view and the ubiquinone is identified as UQ.


As two protons are taken up by ubiquinone, the remaining ones in the proton wire shuffle along the channel and two are added at the other end where it opens to the cytoplasm. (The protons come from the ionization of water.)


Cheng, V.W.T., Johnson, A., Rothery, R.A. and Weiner, J.H. (2008) Alternative Sites for Proton Entry from the Cytoplasm to the Quinone Binding Site in Escherichia coli Succinate Dehydrogenase. Biochemistry 47:9107–9116 [DOI: 10.1021/bi801008e]

Hint

 
In my family we don't give gifts at Christmas (but we do have a Christmas tree and we do celebrate the season). We stopped giving gifts when the children were teenagers and it has eliminated a lot of the stress at this time of year. It also means that we don't have to pretend to like the cheesy presents that we used to get from distant relatives and acquaintances. Not to mention the cheesy ones from spouses.1

However .... if anyone wants to give me a non-Christmas present just for fun, here's an excellent choice: Noah's Ark.


It would look really nice on my office bookshelf. Thanks to PZ Myers for finding this gem. Don't bother getting one for him, he doesn't seem to appreciate the quality workmanship and the attention to detail.


1. Oops, did I say that out loud?

Communicating the Truth about Climate Change

 
There's an ongoing dispute about how to present science to the general public. People like Matt Nisbet and Chris Mooney advocate framing—another word for spin—in order to appeal to the public's perceived biases. They seem to be comfortable with a little "lying for science" as long as it serves the greater good.

Matt Nisbet and Chris Mooney are experts at recognizing that greater good even when others can't see it.

Many scientists—I am one— believe that scientists have to tell the truth no matter how much it might confuse the general public. We believe that evidence-based conclusions are the one thing that separates science from pseudoscience and scientists should never compromise the truth.

Here's an example of how climate change should be presented. It's from an editorial in the Dec. 6 issue of New Scientist [It's the Carbon Stupid].
It's time for heretical thinking on climate change. After two decades in which science has told us more and more about global warming, climate modellers may have to recognise that we have learned most of what we can from their number-crunching.

Some of the detailed forecasts about exactly what the climate will be like in Albuquerque or Basingstoke in 2050 or 2080 are little more than statistical noise, as physicist Lenny Smith underlines this week (see "Bad climate science"). Even the global picture may depend more than we like to admit on feedbacks and tipping points produced by a system that is inherently chaotic. We need to beware of the known unknowns and - whisper it - the unknown unknowns.

Some politicians still demand certainty from climate scientists and are sitting on their hands until they get it. But certainty may be no more available here than in that other troublesome discipline, economics. This is not a counsel for inaction, but for grown-up government: for doing what we know is needed in the face of uncertainty, and for taking actions like those called for this week by the British government's Committee on Climate Change, from decarbonising electricity generation to culling carbon-spewing vehicles and aircraft.

Here's another heresy. Perhaps the endless negotiations to frame a successor to the Kyoto protocol - currently in mid-grind in Poznan, Poland - are becoming an impediment to action. The protocol's various market devices, like cap-and-trade and the clean development mechanism, could now be holding up the technologies we know will do the job. Invented by the Clinton/Gore administration, should they now be jettisoned by Barack Obama? Michael Le Page believes so (see "Time for change on climate: an open letter to Barack Obama") and argues that taxing carbon would be a better plan. It would be a bold move. But just as past economic certainties are failing, maybe it is time to think the unthinkable here too.
The point of this editorial is that there's no reason to be overly alarmist and there's no reason why we can't admit that our climate models are flawed. The bottom line is that we know the climate is warming and we know that we are contributing to the cause. It's time to do something.

The contrasting approach to communicating science is wonderfully described by Matt Nisbet on his blog. Today's posting talks about America's Top Climate Communicator. Matt is not happy with the choices being offered. He proposes his own choice for top climate communicator: the Reverend Richard Cizik, VP for Governmental Affairs of the National Association of Evangelicals.

To back up his nomination Matt quotes from a recent interview ...
GROSS: I imagine you didn't agree with Sarah Palin on environmental issues. For example, her emphasis on drill, baby, drill, and also the fact that she said she wasn't sure if human behavior contributed to climate change. Now, climate change and the environment are issues you're trying to put much more toward the top of the evangelical agenda.

REV. CIZIK: Yeah, I couldn't - you're right. I couldn't have disagreed with her more. Just a year ago, we found out from climate scientists that the melt in the Arctic had turned into a rout. It was happening so fast it was as if your hair turned gray overnight. Now, I have a receding hairline, but I don't have my hair turning gray overnight. Well, that's what happened with the environment. An area the size of Colorado was disappearing every week, and the Northwest Passage was staying wide open all September for the first time in history. And so, to look at this and not see what's happening, I think is, well, it was sort of the ignorance is strength idea. Well, not. It's not strength. Look, strength is knowing what's happening to the world around us, and moreover, as a Christian, we can't claim to love the Creator and abuse the world in which we live. To do so is like claiming to be a fan of Shakespeare and then burn his plays....

...I'm always looking for ways to reframe issues, give the biblical point of view a different slant, if you will, and look it - we have to. The whole world, literally, the planet, is changing around us. And if you don't change the way you think and adapt, especially to things like climate change, scientists like Bob Doppelt, he says, well, if you don't adapt and change your thinking, you may ultimately be a loser because climate change, in his mind, he is a systems analyst, has the capacity to determine the winners and losers, and your life will never be the same, growing up during, I say, the great warming. Our grandparents grew up during the Great Depression. Our parents, well, they lived in the aftermath of that and became probably, the most, well, the greediest generation and our generation, this younger one, needs to be the greenest....
If I have to choose between the New Scientist editorial and Rev. Cizik then New Scientist wins hands down.

What do you think? Is Rev. Cizik going to convince you that he understands the science behind climate change?1


1. The area of Colorado is 269,837 km2 and the area of the entire Arctic ocean is 14,056,000 km2, which 52× the area of Colorado.